The immediate-type hypersensitivities, such as extrinsic asthma, hay fever, and allergic responses to certain food or drugs, are mediated primarily by immunoglobulin E (IgE). In an IgE-mediated allergic response, the allergen binds to IgE on the surface of mast cells and basophilic leukocytes (basophils). This binding causes a crosslinking of the IgE molecules and hence, the underlying receptors for the Fc portion of IgE (Fc.epsilon.R), and thereby triggers the release of pharmacologic mediators, such as histamine, the slow-reacting substance of anaphylaxis, and serotonin. The release of these mast cell and basophil products causes the various pathological manifestations of allergy.
IgE is produced by a particular class of B lymphocytes (B cells), which also bear IgE on their surface. If sensitized to specific allergens, the allergenspecific IgE is produced by B cells continuously.
IgE binds to the receptors for the Fc of IgE (Fc.epsilon.R) on the surface of basophils and mast cells very strongly. The association constant, Ka, is in the neighborhood of 1.times.10.sup.10 liter/mole and the "off" time is more than 20 hour. The very strong and stable association of IgE with Fc.epsilon.R means that IgE is virtually always present on these cells. An immunotherapeutic agent targeting the IgE on B cells must not react with the IgE on basophils and mast cells. Antibodies which react with the IgE isotype will cross-link IgE and the underlying Fc.epsilon.R on basophils and mast cells and, when administered in vivo, will induce systemic release of pharmacologic mediators, leading to allergic symptoms and possibly anaphylaxis.
The development of monoclonal antibodies that recognize an antigenic epitope present on the IgE on B cells, but not the IgE on basophils, was described in U.S. Pat. No. 5,091,313. The method of using such antibodies for assaying for IgE-bearing B cells and for treating type I hypersensitivities is described therein. These antibodies can cause the pharmacological mechanism of antibody-dependent cellular cytotoxicity (ADCC) or complement mediated cytolysis, and thereby down-regulate or lyse IgE-producing B cells and thereby reduce or eliminate IgE. These mechanisms will not induce histamine release from the basophils and mast cells.
If a vaccine was developed which induced production of antibodies which could specifically target IgE-bearing B cells, without targeting any other cells, such a vaccine would be useful in treating allergy and related hypersensitivities. It has been observed that IgE is not needed for normal health, except perhaps for combatting parasites. Thus, depleting all IgE-bearing B cells would not produce any adverse effects.
Dogs are succeptible to a variety of allergies, among the more common forms being tick allergy and flea allergy dermatitis. The latter can be a serious problem in some dogs, as the allergic regions itch and dogs which scratch excessively produce bleeding open sores. The sores are uncomfortable for the afflicted dogs and can become infected.